1. Field of the Invention
This invention relates to a process for the racemization of optically active 4-phenylbutanoic acid esters of the general formula (1) ##STR2## wherein R.sup.1 represents a hydroxy group, a hydroxy group protected by vinyl ether, or a lower acyloxy group and R.sup.2 represents a lower alkyl group.
Optically active 2-hydroxy-4-phenylbutanoic acid esters or derivatives thereof included in the aforementioned general formula (1) are useful as a starting substance for the synthesis of pharmaceuticals like angiotensin converting enzyme-inhibiting pharmaceuticals, such as Cilazapril, Quinapril, Enalapril, Indolapril, Ramipril, and Lisinopril.
2. Description of the Prior Art
A process for the racemization of optically active 4-phenylbutanoic acid esters in which 2-position is replaced by a hydroxy group, a hydroxy group protected by vinyl ether, or a lower acyloxy group has not been reported until today.
When optically inactive (.+-.)-2-hydroxy-4-phenylbutanoic acid esters which can be synthesized by a following method are used as a starting substance for the preparation of aforementioned pharmaceuticals, the racemate must be optically resolved to separate into one conformation such as R(-)-2-hydroxy-4-phenylbutanoic acid esters concerning the conformation of hydroxy group at 2-position.
Heretofore, the following two methods have been reported concerning optically resolving (.+-.)-2-hydroxy-4-phenylbutanoic acid or esters thereof into its optically active forms respectively. One method is treating (.+-.)-2-hydroxy-4-phenylbutanoic acid with an optically active menthol to form its menthyl esters, repeating recrystallization from petroleum ether to obtain an optically active menthyl ester (refer to "Optical Resolution Procedures for Chemical Compounds" pp 476 (1986) published by OPTICAL RESOLUTION INFORMATION CENTER, Manhattan Colledge, Riverdale, N.Y.); and the other method is treating (.+-.)-2-hydroxy-4-phenylbutanoic acid with an optically active 1-(p-tolyl)ethylene amine or an optically active N-(2-hydroxy)ethyl-.alpha.-methylbenzyl amine as a resolving agent (refer to EP 0329156).
However, since a method for the racemization of optically active 2-hydroxy-4-phenylbutanoic acid and optically active 2-hydroxy-4-phenylbutanoic acid esters have not been reported heretofore, the useless optically active compound in the other form, recovered at the optical resolution of (.+-.)-2-hydroxy-4-phenylbutanoic acid esters, has not been effectively utilized.
Accordingly, the object of the present invention is to provide a process for racemizing optically active 4-phenylbutanoic acid esters effectively and easily.